What tests are used to diagnose pulmonary tuberculosis (TB)?

Diagnostic Tests for Pulmonary Tuberculosis

All persons suspected of having pulmonary tuberculosis should have sputum specimens submitted for AFB smear microscopy, rapid molecular testing (NAAT), and both liquid and solid mycobacterial cultures in a quality-assured laboratory. 1

Essential Diagnostic Testing Algorithm

Sputum Collection and AFB Smear Microscopy

• Collect at least three sputum specimens (8-24 hours apart), with at least one early morning specimen, for all patients with suspected pulmonary TB 1
• Request a sputum volume of at least 3 mL, optimally 5-10 mL for each specimen 1
• Use concentrated specimens and fluorescence microscopy as these increase sensitivity by 18% and 10% respectively compared to non-concentrated specimens and conventional microscopy 1
• The first specimen has 53.8% sensitivity, the second adds 11.1%, and the third adds only 2-5% additional yield 1
• Early morning specimens are 12% more sensitive than spot specimens 1

Critical caveat: A negative AFB smear does NOT exclude pulmonary TB—approximately 30-40% of culture-confirmed TB cases are smear-negative 2, 3, 4

Rapid Molecular Testing (NAAT)

• Perform NAAT (such as Xpert MTB/RIF or GeneXpert) on at least one initial respiratory specimen, preferably the first diagnostic specimen 1, 2
• NAAT provides results within 1-2 days and simultaneously detects rifampin resistance as a marker for multidrug-resistant TB 1, 2
• In smear-positive patients, a positive NAAT confirms TB; in smear-negative patients with intermediate to high suspicion, a positive NAAT serves as presumptive evidence 1
• A negative NAAT cannot exclude pulmonary TB, particularly in smear-negative cases 1, 3

Mycobacterial Culture (Gold Standard)

• Perform both liquid and solid mycobacterial cultures on every specimen from patients with suspected TB 1
• Liquid cultures have 88-90% sensitivity compared to 76% for solid cultures alone, with shorter time to detection (10-14 days vs. 25.8 days) 1, 4
• Culture allows for species identification and comprehensive drug susceptibility testing (DST) to first-line and second-line agents 1, 2
• Three consecutive negative cultures from adequate specimens effectively exclude pulmonary TB in most cases 4

Chest Radiography

• Obtain chest X-ray in all patients with suspected pulmonary TB to assess for findings suggestive of disease (upper lobe infiltrates, cavitation, nodular patterns) 1, 2, 3
• Chest radiographic findings alone have low specificity (66%) and should not be used without bacteriological confirmation 5
• Consider CT imaging when chest radiograph is normal or inconclusive but clinical suspicion remains high 3

Drug Susceptibility Testing

• Perform DST to first-line drugs on all initial isolates using both rapid molecular methods and culture-based techniques 1, 2
• Rapid molecular tests for resistance markers should be available with 1-2 day turnaround time 1
• Failure to perform DST can lead to inappropriate treatment regimens and development of further resistance 2

Special Diagnostic Situations

Patients Unable to Produce Sputum

• Attempt sputum induction with hypertonic saline before considering invasive procedures 1, 2, 4
• If sputum induction fails, perform bronchoscopy with bronchoalveolar lavage plus brushings 1, 2
• Collect post-bronchoscopy sputum specimens from all patients who undergo bronchoscopy 2

Children with Suspected Pulmonary TB

• Obtain specimens through expectorated or induced sputum, bronchial secretions, gastric washings, or endoscopic ultrasound-guided biopsy 1
• Gastric aspirates (three consecutive morning specimens) can yield 40-50% positivity in children unable to produce sputum 3, 4
• In children with negative bacteriological results, diagnosis may be based on chest radiography abnormalities, history of exposure, positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA), and clinical findings 1

HIV-Infected Patients

• Maintain a lower threshold for bronchoscopy due to atypical presentations and lower smear sensitivity 3
• All patients with confirmed pulmonary TB should be offered HIV testing due to high co-infection rates and impact on management 2
• NAAT sensitivity in HIV-infected patients is approximately 79% compared to 89% in HIV-negative patients 1

Culture-Negative Pulmonary TB Diagnosis

When all bacteriological tests are negative (smear, culture, NAAT), diagnosis should be based on: 1

• Chest radiographic findings compatible with tuberculosis
• Lack of response to a trial of broad-spectrum antimicrobial agents (avoid fluoroquinolones as they have anti-TB activity and may cause transient improvement)
• In seriously ill patients or those with HIV/immunocompromising conditions, expedite evaluation and initiate anti-TB treatment if clinical evidence strongly suggests TB

Additional Baseline Testing

• Perform HIV testing in all patients with confirmed pulmonary TB 2
• Obtain baseline laboratory tests including complete blood count, liver function tests, and kidney function tests before initiating treatment 2

Common Diagnostic Pitfalls

• Never rely on a single negative sputum specimen to exclude TB—three specimens are required 3, 4
• Do not use TST or IGRA to exclude active TB disease—these tests detect latent infection, not active disease 1, 3, 4
• Do not assume negative AFB smears exclude TB—40% of culture-positive cases are smear-negative 3, 4
• Insufficient sputum quantity or quality leads to false-negative results; proper collection technique is essential 2, 3
• Do not delay empiric treatment in seriously ill patients while awaiting culture results if clinical suspicion is high 1, 3
• Always collect specimens for culture and DST before starting treatment, as this guides definitive therapy 3